Polycystic Ovary Syndrome (PCOS)

Overview

What Is It?

Polycystic ovary syndrome (PCOS) is generally characterized by the presence of polycystic ovaries, hyperandrogenism (the condition caused by excess male hormones or male-like traits) and irregular ovulation and menstruation.

Polycystic ovary syndrome (PCOS) is the most common hormone abnormality of reproductive-age women, the most common cause of infertility in women and an important harbinger of metabolic disorders such as diabetes and heart disease. It affects an estimated 5 percent to 10 percent of females and is associated with an increased risk of diabetes and obesity, and possibly an increased risk of stroke and cardiovascular disease. The syndrome is generally characterized by the presence of polycystic ovaries, hyperandrogenism (the condition caused by excess male hormones or male-like traits), and irregular ovulation and menstruation. The symptoms of PCOS can vary.

The syndrome was previously called Stein-Leventhal Syndrome after the physicians who first characterized it in the 1930s. Although its cause remains unknown, it usually presents in young women or adolescents, and the main symptoms are irregular or absent periods and excess unwanted facial and/or body hair growth (hirsutism). As the term "polycystic ovary syndrome" suggests, the disorder is often accompanied by enlarged ovaries containing multiple small painless benign "cysts" or tiny follicles about 1/8 to 1/4 inch in diameter.

During a normal menstrual cycle in which a woman ovulates (called an ovulatory cycle), a small number of follicles begin to grow. One becomes the biggest, or dominant, follicle. This dominant follicle then ruptures and releases the egg.

In women with PCOS, the hypothalamic-pituitary (in the brain) functions abnormally, and high levels of hormones called androgens (commonly known as "male hormones") disturb the ovulatory process, halting the normal development of the sacs, called follicles, that contain each individual egg (or ova). These halted or arrested follicles––whose appearance (via an ultrasound) is sometimes likened to a "string of pearls" on the outside border of the ovary––form the "cysts" observed in PCOS. These cysts are not tumors and do not require removal.

Treatment of PCOS, instead, is through the use of lifestyle modifications and medication to treat symptoms.

Many, but not all, women with PCOS will have the polycystic-looking ovaries (which are often two to five times larger than normal ovaries) for which the syndrome is named, but it is possible to be diagnosed with the syndrome without having this sign. And not all women with polycystic-appearing ovaries will have PCOS.

Many women with PCOS experience excess insulin production from the pancreas, which can result from insulin resistance, meaning that their cells don't respond well to insulin, so the insulin has difficulty working in their bodies. Hence, higher levels of insulin are needed to maintain normal glucose and lipid levels. Insulin, a hormone produced by the pancreas, regulates a range of functions, including controlling blood sugar (glucose) and fats (lipids).

Insulin resistance can lead to hyperinsulinism or hyperinsulinemia. It is also a precursor to type 2 diabetes. Furthermore, the high levels of insulin help stimulate the ovaries to overproduce androgens, which may be the cause of PCOS in some women.

In addition to stimulating the ovaries to overproduce androgens, high levels of insulin can cause darkening of the skin around the neck and other crease areas, a condition called acanthosis nigricans, often accompanied by skin tags in these areas.

If the pancreas can't produce enough insulin to compensate for the insulin resistance, glucose builds up in the blood, eventually leading to type 2 diabetes.

Up to 75 percent of women with PCOS have insulin resistance and about 10 percent develop type 2 diabetes by age 40. Insulin resistance and an increased risk of diabetes are major problems for obese women with PCOS, but they also cause problems for normal weight women with PCOS. For obese women with PCOS, treatment plans should incorporate diet and exercise.

Obesity in women with PCOS tends to be centered on the abdomen, a fat distribution pattern linked to increased risk of diabetes, heart disease and high blood pressure.

Up to 50 percent of women with PCOS also have sleep apnea, a condition that causes brief spells where breathing stops during sleep. Sleep apnea can worsen the degree of insulin resistance.

The most visible symptoms of PCOS stem from excessive levels of androgens, such as testosterone, produced by the ovaries and the adrenal glands. Androgens often are called "male hormones," even though they are found in both men and women. They are usually present at higher concentrations in men and are an important factor in determining male traits and reproductive activity. Androgens, or androgen precursors, include testosterone, dihydrotestosterone (DHT), androstenedione, dehydroepiandrosterone (DHEA) or DHEA sulfate (DHEA-S).

Excessive levels of these hormones, a condition called hyperandrogenemia, or their exaggerated action, called hyperandrogenism can lead to some of the most common symptoms of PCOS in women, including:

• Excess body or facial hair (hirsutism)
• Oily skin and acne
• Oligo-ovulation (irregular ovulation and menstruation)
• Scalp hair loss and balding (male pattern balding and androgenic alopecia)

But such symptoms alone are not enough to support a diagnosis of PCOS. They may only indicate the presence of hyperandrogenism, which can result from several conditions.

Women with PCOS ovulate irregularly and/or infrequently and often have irregular menstrual periods. Inducing a period is important because the hormone progesterone promotes the normal shedding of the uterine lining (i.e., menstruation), preventing the buildup of the uterine lining, and reducing the risk of endometrial (uterine) cancer. However, progesterone is secreted by the ovaries only after ovulation occurs, so progesterone may need to be administrated to women with PCOS either alone regularly or as part of a combination hormonal contraceptive.

PCOS often is a cause of infertility due to a failure to ovulate.

Women with PCOS are more likely to be overweight or obese, although the exact relationship of PCOS and body weight is unknown. Excess weight worsens PCOS, but researchers do not yet know whether or not having PCOS makes patients more prone to obesity.

It is not surprising that women with PCOS often suffer from poor self image and may experience depression or anxiety.
While the biochemical imbalances that cause symptoms are becoming better understood, the trigger or triggers for PCOS remain unknown. Most believe PCOS results from genetic defects, often in combination with environmental factors. Genetic defects may result in abnormal function of the hormones from the pituitary that regulate ovulation (LH and FSH), in abnormal development of the follicle, in increased production of male hormones (androgens), and in insulin resistance and excessive production of insulin. All these prevent the ovaries from functioning normally.

Because PCOS is mostly a genetic disorder, the risk of PCOS in family members is high. For example, an estimated 30 percent of mothers, and 50 percent of sisters and daughters of people with PCOS can be affected.

To date there is no cure for PCOS. Health care professionals can usually address the most bothersome symptoms. Because of the complexity of the hormonal interactions, you may need to see an endocrinologist. You may also need to visit a reproductive endocrinologist, especially if you are infertile and trying to conceive. Not all physicians have experience treating PCOS, so check with the doctor's office to see if that doctor cares for many people with PCOS.

Diagnosis

Diagnosis begins with an inventory of signs and symptoms, the most common of which are:

• Unwanted hair growth or hirsutism (excess body and/or facial hair in a male-like pattern, particularly on the chin, upper lip, breasts, inner thighs and abdomen)
• Irregular or infrequent periods
• Obesity, primarily around the abdomen (although only about 30 percent to 60 percent of patients are obese)
• Acne and/or oily skin (particularly severe acne in teenagers or acne that persists into adulthood)
• Infertility
• Ovarian appearance suggesting polycystic ovaries
• Hair loss or balding
• Acanthosis nigricans (darkening of the skin, usually on the neck; also a sign of insulin problems), often with skin tags (small tags of excess skin), most often seen in the armpit or neck area

Women with PCOS may have varying combinations of these and other signs and symptoms, but three important features of the disorder include the following:

• Hyperandrogenism (signs of male-like traits, such as hirsutism) and/or hyperandrogenemia (excess blood levels of androgens). Androgens are hormones such as testosterone that in excess quantities cause such symptoms as hirsutism and acne. In more severe cases, "virilization"––taking on significant male characteristics, including severe excess facial and body hair, an enlarged clitoris, baldness at the temples, acne, deepening of the voice, increased muscularity and an increased sex drive––may occur. However, virilization is more frequently a sign of an androgen-producing tumor, which should be searched for.

• Lack of ovulation or irregular ovulation often resulting in irregular or absent menstruation. Women with PCOS usually have oligomenorrhea (eight or fewer periods per year) or amenorrhea (absence of periods for extended periods).

• Polycystic ovaries on ultrasound

Expert groups have determined that a woman must exhibit at least two of these three symptoms to be diagnosed with PCOS.

The diagnostic process should include a thorough physical examination and history to check for signs and symptoms of other disorders that can have similar signs and symptoms, such as hypothyroidism, Cushing's syndrome (a hormonal disorder in which the adrenal glands malfunction), adrenal hyperplasia (a genetic condition that results in male hormone excess produced by the adrenal glands), and androgen-secreting tumors (of the ovary, adrenal gland, etc.).

While there is no single test for PCOS, a health care professional may measure blood levels of the following:

• Thyroid hormone (symptoms of low thyroid function, or hypothyroidism, include irregular menstruation, similar to that of PCOS)
• Prolactin (high levels of this hormone, which stimulates milk production, often results in irregular or absent menses similar to that seen in PCOS)
• Level of 17-hydroxyprogesterone, a marker for the most common cause of adrenal hyperplasia (due to 21-hydroxylase deficiency). If the screening level is high, your doctor may choose to perform an adrenal stimulation test.
• Androgen levels, including total and free testosterone and dehydroepiandrosterone sulfate (DHEAS). Androgen-producing tumors, although they are rare, can result in some of the masculinizing symptoms of PCOS. If your testosterone level is persistently very high, your health care professional may want to investigate further.
• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. FSH promotes the development of egg-containing follicles in the ovaries, while LH stimulates ovulation as well as follicle rupture and encourages the empty follicle to convert to progesterone production. A high ratio of LH to FSH (greater than 2:1 or 3:1) may be characteristic of PCOS, although women with PCOS can also have normal FSH and LH levels and a normal ratio, so FSH and LH testing is not always useful in diagnosing PCOS.
• A two-hour glucose tolerance test. This test, where your blood is drawn before you drink a sugary solution and again one and two hours afterward, should be performed in all women diagnosed with PCOS, because diabetes or prediabetes is hard to detect in many women with PCOS without this test.
• Physicians may also order tests to measure blood fat (lipid) and cholesterol levels.

These tests should be interpreted carefully by a specialist. The best time to be tested is in the morning just after your menstrual period begins (you may need medication to induce menstruation). Birth control pills might make the tests difficult to interpret because they change the hormonal balance and may mask any abnormalities that may exist in male hormones.

• Your health care professional may order ultrasound imaging of the ovaries to look for the characteristic picture of multiple cysts. An ultrasound may also be used to look for abnormalities in the lining of the uterus, called the endometrium.

The ultrasound test usually involves insertion of a probe into the vagina, although a transabdominal ultrasound, in which the ultrasound is passed over your abdomen, can be performed, particularly in women who have never been sexually active.

PCOS is also associated with an increased risk of diabetes and obesity, and as a result, an increased risk of cardiovascular disease. If you have PCOS, you should be tested and treated for insulin resistance, type 2 diabetes, high blood pressure and elevated blood lipids (cholesterol and triglycerides). Women with PCOS who become pregnant should be advised that they are at increased risk of developing gestational diabetes.

Treatment

Treatment of polycystic ovarian syndrome (PCOS) centers on lifestyle modifications and medication. Surgical procedures to destroy or shrink the ovarian cysts are less likely to be performed today given the success of hormonal treatments. However, if you fail to ovulate with conventional treatment (the fertility drug clomiphene citrate (Clomid)) and can't, for whatever reason, proceed to gonadotropin shots or in vitro fertilization (IVF), your doctor may recommend an outpatient surgery called laparoscopic ovarian drilling.

Because the primary cause of PCOS is unknown, treatment is directed at the primary symptoms of the disorder, which include excess hair growth, irregular periods and infertility.

Excess hair growth

For some women, the most bothersome symptom is hirsutism (excess facial and/or body hair, often dark and coarse). This symptom, as well as acne and oily skin, stem from the overproduction of androgens. For women with these symptoms, an anti-androgen medication like spironolactone, finasteride or flutamide may be prescribed.

Spironolactone is a diuretic that works by blocking the action of testosterone at the hair follicle. Side effects are generally mild and may include heartburn and upset stomach, sun sensitivity, increased urination and lower blood pressure causing weakness or faintness. At high doses, it can clear oily skin and make unwanted hair finer.

Finastride, which is used to treat enlarged prostate and baldness in men, may also be useful in women with hyperandrogenism symptoms, including hirsutism. It may also help treat hair loss on the scalp associated with PCOS. Finasteride, however, can cause birth defects in a male fetus (pregnant women should not even handle the drug in crushed tablet form). And many insurance companies won't cover the drug for cosmetic reasons.

Flutamide, a drug used to treat prostate cancer in men, is also useful for the treatment of signs and symptoms due to hyperandrogenism in women with PCOS, although it carries the rare risk of liver toxicity.

If you are trying to conceive, you cannot take an anti-androgen medication because it could cross the placenta and cause defects in a male fetus. Usually, anti-androgen medications are used in combination with birth control pills, which not only prevent unplanned pregnancies, but also improve the success of these medications on excess hair growth.

None of these drugs is FDA-approved for the treatment of PCOS, but clinical experience and scientific study has shown that they can be effective.

Electrolysis, and possibly lasers, can remove any remaining hairs permanently.

Eflornithine hydrochloride cream (Vaniqa) may also help slow the hair growth on the face. It works well in about one-third to one-half of women using it. The medication is applied to the face twice a day like a moisturizer. It works by blocking a key enzyme that makes hair grow. Noticeable results take about six to eight weeks. It must be used regularly or the hair will grow back after about eight weeks.

Bear in mind that it can take up to nine months to see effects on hair growth and a year or longer to achieve peak effect. The hair will still be there, but it will generally grow more slowly and be lighter and finer.

Irregular periods

If irregular and/or infrequent menstruation is a problem, birth control pills that contain estrogen and progestin can generally regulate your cycles. Restoring regular periods is essential since it ensures that the lining of the uterus is shed, protecting against uterine cancer. Birth control pills also reduce the production of androgens by the ovaries.

Rare side effects of birth control pills include migraines, nausea and headaches, and, rarely blood clots (especially among smokers and women with persistent high blood pressure), gallbladder disease and high blood pressure.

If you don't want to take a daily medication, talk to your doctor about a course of progestogen (progesterone-like drugs) several times a year to start your periods. It is important to have at least six to eight periods a year to promote shedding of the endometrial lining; buildup can lead to cancer. However, periodic progesterone alone does not help reduce unwanted hair growth as birth control pills do.

Another drug that helps regulate periods in some women with PCOS, although less effectively than birth control pills, is the insulin-sensitizing drug metformin (Glucophage). Metformin regulates blood glucose (sugar) levels by reducing the amount of glucose the liver produces, reducing the amount of glucose absorbed from food and reducing the levels of insulin in the blood by helping the insulin that your body produces work better to reduce the amount of glucose already in your blood.

The drug is not FDA-approved for PCOS, but research done so far shows it helps modestly improve ovulation and may reduce androgen levels. If you are among the 10 percent or so of women with PCOS who already have type 2 diabetes, metformin is also a good therapeutic option. Experts aren't sure, however, if metformin is as effective at preventing endometrial cancer in women with PCOS as birth control pills or progesterone. In addition, some experts do not recommend metformin for women with PCOS who have excess hair growth (hirsutism).

If you are prescribed metformin, be sure to inform your health care professional of all other medications you are taking, including over-the-counter medicines, to prevent drug interactions.

Infertility

Infertility often is a consequence of PCOS. If you are overweight or obese, the first line of treatment is weight loss; even losing a little bit of weight may stimulate ovulation. Weight loss can also boost the effectiveness of other infertility treatments.

The second line of treatment is the ovulation-stimulating drug clomiphene citrate, which is used to treat infertile women with ovulation problems. It works by helping the pituitary gland send hormonal signals to stimulate the development of more eggs in the ovaries. Clomiphene stimulates ovulation in about 80 percent of women with PCOS, and about half of these women become pregnant.

Another option for women with PCOS who do not ovulate is letrozole, a medication FDA-approved for breast cancer treatment. Letrozole is sometimes used off label to induce ovulation. Some studies have shown live birth rates in obese women with PCOS who take letrozole are higher than in obese women with PCOS who take clomiphene.

If clomiphene doesn't work, your doctor may suggest using metformin in combination with clomiphene or gonadotropins injections.

Treatment with gonadotropins—purified solutions of follicle-stimulating hormone (FSH) with or without luteinizing hormone (LH)—may be administered by injection. Because many women with PCOS have elevated LH, some doctors may recommend treatment with FSH alone.

But treatment with gonadotropins, while effective, is more challenging to manage and more expensive. Some women also have some trouble self-administering the injections. Risks include multiple births and ovarian hyperstimulation syndrome. In many patients mild signs and symptoms of hyperstimulation may occur, including bloating, fluid retention, weight gain and a tender stomach. In more severe cases fluid from the bloodstream leaks into the abdominal cavity, causing it to swell, and making the blood thicker. This may lead to breathing difficulties, temporary kidney failure and blood clots. Thus, gonadotropins should only be prescribed by clinicians specifically trained in their use.

Another option for women who fail to ovulate with clomiphene or metformin therapy, or who are unwilling or unable to use gonadotropins (or can't afford to use them), is a surgical procedure known as laparoscopic ovarian drilling.

During this procedure, a surgeon makes a small incision in your abdomen and inserts a laparoscope (a telescope-like instrument attached to a tiny camera). The surgeon then makes other small incisions and inserts surgical equipment that uses electrical or laser energy to burn small holes in the enlarged follicles on the surface of your ovaries. The goal of the procedure is to stimulate ovulation by reducing LH and androgen levels.

Additionally, many women who failed to ovulate with clomiphene or metformin therapy are able to ovulate with these medications after ovarian drilling. The success rates for laparoscopic ovarian drilling appear to be better for patients at or near their ideal body weight, as opposed to those who are obese. Interestingly, women in these studies who are smokers rarely improved with the drilling procedure. Side effects are rare, primarily adhesions, although laparoscopic ovarian surgery requires general anesthesia, which carries its own risks.

Other Approaches

Long-term, nonmedical treatment is geared toward modifying your risk factors for health problems often associated with PCOS, including diabetes, uncontrollable weight gain and heart disease. A healthy, low-sugar, low-starch diet and an exercise program to stabilize your weight can reduce the risk of these conditions.

You can manage some problems associated with PCOS without medication. Excess hair can be removed by shaving, tweezing, waxing or using depilatory creams, or by electrolysis or laser techniques administered by a trained professional. Since lasers work by attacking a skin pigment, they should be used with caution by darker-skinned women.

If you are overweight and have PCOS, you need to lose weight. Losing even just a small amount of weight can lower androgen and insulin levels, reducing your risk of insulin resistance and diabetes. Some obese women with PCOS find losing just 5 to 10 percent of their body weight helps their periods become more regular.

Exercise alone, even without weight loss, is also beneficial since it helps improve insulin sensitivity.

It seems that some PCOS symptoms improve as women near menopause, but some of the complications may persist into or beyond menopause, particularly male pattern baldness or thinning hair, which sometimes gets worse after menopause. The risk for heart attack, stroke and diabetes also increases in menopause in women with PCOS. In cases where PCOS symptoms persist, the best recommendation is to monitor cholesterol, triglycerides and blood pressure, as well as glucose and insulin levels.

Prevention

There is no known way to prevent polycystic ovary syndrome (PCOS). Researchers are still working to understand the underlying causes. However, if you have PCOS there is a high likelihood that your daughter or sister will have the disorder. There are steps you can take to prevent some of the worst consequences of the disorder––diabetes, uterine cancer, high blood pressure and high levels of blood lipids (a risk factor for heart disease).

If you do not menstruate, inducing menstruation with a progesterone-like agent should be a top priority. During menstruation, the endometrial lining is shed in response to withdrawal of the progesterone hormone. Without this shedding, your risk of uterine cancer rises significantly. Birth control pills, which combine estrogen and progestin, can restore regular periods. If you don't want to take a daily medication, a course of progesterone, such as medroxyprogesterone acetate, micronized progesterone or norethindrone acetate, taken for 10 to 14 days every one to three months, may help.

If you are overweight, losing weight is a big step toward lowering your risk for diabetes and heart disease. Losing weight can help restore regular periods and improve other hormonal imbalances, but weight loss is often an incomplete solution to PCOS.

Facts to Know

1. Polycystic ovary syndrome (PCOS) is the most common endocrine disturbance in women of reproductive age, affecting an estimated 5 percent to 15 percent of all women.
   
2. No one knows exactly what causes PCOS, although evidence suggests a definite genetic link to the disorder.
3. Many women with PCOS will have polycystic ovaries, but it is possible to be diagnosed with the syndrome without this sign, and not all women with polycystic-appearing ovaries will have PCOS.
4. Many PCOS symptoms are the result of high levels of androgens. These hormones are often called "male hormones" even though they are found in both men and women. Androgens include testosterone, DHT, androstenedione and DHEA. Other hormones can be converted into testosterone or DHT.
5. About half of women with PCOS experience gradual weight gain and obesity. In some women with PCOS, obesity develops around the time of puberty.
6. PCOS is strongly linked to insulin resistance (a precursor to type 2 diabetes and heart disease). For women with PCOS who are obese, the treatment plan should incorporate a diet and exercise program. By age 40, about 35 percent of women with PCOS who are obese have impaired glucose tolerance (pre diabetes), and about 10 percent have type 2 diabetes. However, not all women who have PCOS are insulin-resistant or diabetic.
7. Women with PCOS are at increased risk for developing type 2 diabetes and obesity, and as a result have an increased risk of cardiovascular disease.
8. If you are overweight, losing weight is a major step toward lowering your risk for diabetes and heart disease. Losing weight can help restore regular periods and improve other hormonal imbalances, but weight loss is often an incomplete solution to PCOS.
9. If irregular and/or infrequent menstruation is a problem, birth control pills or periodic courses of a progestin alone can probably get you on schedule again. During menstruation, the lining of the uterus is shed, providing protection against uterine cancer, so restoring regular periods is important.
10. Occasionally, PCOS symptoms are the result of an androgen-producing tumor. If symptoms are severe or progress rapidly, or your testosterone level is very high or your cortisol level is elevated, your health care professional may want to investigate further.

Questions to Ask

Review the following Questions to Ask about polycystic ovary syndrome (PCOS) so you're prepared to discuss this important health issue with your health care professional.

1. How much experience do you have diagnosing and treating PCOS? If you don't have a lot of experience, can you recommend a specialist?
2. How long will it take to see effects from my medications? How dramatic can I expect the effects to be?
3. What are the side effects of these medications? How can I spot them early?
4. How do you feel about prescribing insulin sensitizers?
5. I don't want to take birth control pills. What alternatives can you recommend?
6. Is it safe to get pregnant or breastfeed on these medications?
7. What steps should I take if I decide I want to get pregnant?
8. Can you recommend any lifestyle changes that might make a difference in my condition? How big a change can I expect?
9. For my skin color and type, what is an optimal hair removal method?
10. How does PCOS affect my other health conditions?

Key Q&A

Organizations and Support

For information and support on coping with Polycystic Ovary Syndrome, please see the recommended organizations, books and Spanish-language resources listed below.

American Society for Reproductive Medicine (ASRM)
Website: https://www.asrm.org
Address: 1209 Montgomery Highway
Birmingham, AL 35216
Phone: 205-978-5000
Email: asrm@asrm.org

Polycystic Ovarian Syndrome Association
Website: https://www.pcosupport.org
Address: P.O. Box 3403
Englewood, CO 80111
Hotline: 1-877-775-PCOS (1-877-775-7267)
Email: info@pcosupport.org

Books

A Gynecologist's Second Opinion
by William H. Parker and Rachel L. Parker

Pocket PCOS: A Quick and Practical Guide to Polycystic Ovary Syndrome with Personal Testimonies
by Christopher Hearn and M.D. Shahab S. Minassian

Spanish-language resources

Medline Plus: Ovarian Cysts
Website: https://www.nlm.nih.gov/medlineplus/spanish/ovariancysts.html
Address: Customer Service
8600 Rockville Pike
Bethesda, MD 20894
Email: custserv@nlm.nih.gov

American Academy of Family Physicians
Website: https://familydoctor.org/online/famdoces/home/women/reproductive/gynecologic/279.printerview.html